Inflammatory Disease as Chronic Stress

Abstract

It is now established that communication between the CNS and the immune system is bidirectional, that endocrine factors can alter immune function and that immune responses can alter both endocrine and CNS responses. In many respects CNS and endocrine responses to acute inflammation are similar to the changes associated with acute stress exposure. In contrast, during chronic inflammation associated with adjuvant induced arthritis (AA), although circulating levels of corticosterone are increased, the peptidergic regulation of the hypothalamus is different from that seen during acute stress. As the disease progresses, a paradoxical reduction occurs in CRH mRNA in the paraventricular nucleus (PVN), whereas PVN AVP mRNA increases. These data suggest that there is increased expression of AVP mRNA within the CRH cells of the PVN with an increased emphasis on AVP regulation of HPA output. Additionally, HPA function is altered during chronic inflammation such that responses to psychological stress (i.e. restraint) are significantly dampened, while responses to further inflammatory challenges are maintained. These data suggest that alterations in PVN peptide colocalization may be important in regulating the progression of peripheral inflammatory responses and that the effects of inflammation on the hypothalamus alter stress-responsive systems. In addition to the AA model, we have similarly observed alterations in PVN peptide mRNA expression with disease onset in the murine MRL lpr/lpr and MRL +/+ model of SLE. Disease onset in murine SLE is spontaneous and does not rely on exogenous application of adjuvant; however, decreased levels of CRH in the PVN were observed from early disease onset in this animal model. It is suggested that alterations in CRH regulation in response to either acute or chronic inflammation may contribute as etiological factors to both psychiatric (i.e. neuropsychiatric SLE) and stress-related disease.

Captivity induces hyper-inflammation in the house sparrow (Passer domesticus)

“…Importantly, only wild birds released CORT in response to LPS; captive birds did not. CORT is integral to the downregulation of inflammation (Shanks et al, 1998), and although baseline GCs were not elevated significantly in captive birds in the present study, in prior studies, captivity decreased expression of both glucocorticoid and mineralocorticoid receptors, increased baseline CORT and prevented further CORT release in response to a restraint stressor (Kuhlman and Martin, 2010) (L.B.M., A. Urban, C.A.C.C.…”

“…Future studies could evaluate whether the many ailments presently associated with chronic stress and/or disregulation of GCs in human populations (e.g. obesity, diabetes and rheumatoid arthritis) (Glaser and Kiecolt-Glaser, 2005;Shanks et al, 1998) occur in for animals in zoos, aquaria and captive breeding and translocation programs.…”

Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation

“…Despite the compelling support for a model integrating psychological and physiological factors in asthma, the brain has been largely absent from any discussion of its mechanistic underpinnings. The extant literature indicates that both physiological and psychological stressors activate similar neural circuitry, acting as two different routes to a bidirectional communication network between the brain and the immune system (5,6). Consistent with this model, neural circuitry underlying stress and emotion can regulate inflammation (7,8), and peripheral inflammatory mediators can influence mood and cognitive function (9).…”

Site-specific overexpression of corticotropin-releasing hormone (CRH) in the mouse brain – modelling central CRH system hyperactivity

“…Some stress paradigms (e.g. adjuvant-induced arthritis) that continuously activate the HPA axis are actually associated with reductions in central CRH drive, but concomitant increases in AVP drive on the pituitary (Harbuz et al, 1997) (Shanks et al, 1998).…”